Q9Y3S1 (WNK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase WNK2
EC=2.7.11.1

Alternative name(s):
Antigen NY-CO-43
Protein kinase lysine-deficient 2
Protein kinase with no lysine 2
Serologically defined colon cancer antigen 43

Gene names

Name:	WNK2
Synonyms:	KIAA1760, PRKWNK2, SDCCAG43
ORF Names:	P/OKcl.13

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	2297 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5. Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression. Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1. WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity. Ref.8 Ref.10 Ref.13
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity. UniProtKB Q9H4A3
Enzyme regulation	Activation requires autophosphorylation of Ser-356. Phosphorylation of Ser-352 also promotes increased activity By similarity. UniProtKB Q9JIH7
Subunit structure	Forms a complex with the phosphorylated form of STK39 By similarity.
Subcellular location	Cytoplasm. Cell membrane Ref.8 Ref.10.
Tissue specificity	Expressed in various cancer cell lines (at protein level). Predominantly expressed in heart, brain, skeletal muscle and colon. Ref.1 Ref.8 Ref.13
Post-translational modification	Autophosphorylated. Ref.8 Ref.10 Ref.13
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. Contains 1 protein kinase domain.
Caution	Cys-224 is present instead of the conserved Lys which is expected to be an active site residue. Lys-207 appears to fulfill the required catalytic function. UniProtKB Q9JIH7
Sequence caution	The sequence AAH37965.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype Ref.8. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of sodium ion transmembrane transporter activity Inferred from mutant phenotype Ref.13. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.8. Source: UniProtKB regulation of ion homeostasis Inferred from mutant phenotype Ref.13. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.8. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 (identifier: Q9Y3S1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 Ref.5 (identifier: Q9Y3S1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1345-1381: Missing.
     2247-2261: DGALGTARRNQVWFG → GSCGPRAVSTPTSYT
     2262-2297: Missing.

Note: No experimental confirmation available.

Isoform 3 Ref.4 (identifier: Q9Y3S1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
     680-731: Missing.
     843-845: LAA → RTR
     846-2297: Missing.

Note: Incomplete sequence.

Isoform 4 Ref.7 (identifier: Q9Y3S1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     2248-2254: GALGTAR → PESEKPD
     2255-2297: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2297	2297	Serine/threonine-protein kinase WNK2		PRO_0000086822
Regions
	Domain	195 – 453	259	Protein kinase
	Nucleotide binding	201 – 209	9	ATP By similarity UniProtKB Q8TDX7
Sites
	Active site	323	1	Proton acceptor By similarity UniProtKB Q8TDX7
	Binding site	207	1	ATP By similarity UniProtKB Q9JIH7
Amino acid modifications
	Modified residue	45	1	Phosphoserine Ref.13
	Modified residue	352	1	Phosphoserine; by autocatalysis By similarity UniProtKB Q9JIH7
	Modified residue	356	1	Phosphoserine; by autocatalysis By similarity UniProtKB Q9JIH7
	Modified residue	560	1	Phosphoserine Ref.13
	Modified residue	1150	1	Phosphoserine Ref.13
	Modified residue	1262	1	Phosphoserine Ref.13
	Modified residue	1588	1	Phosphoserine Ref.13
	Modified residue	1685	1	Phosphoserine Ref.13
	Modified residue	1736	1	Phosphoserine Ref.13
	Modified residue	1817	1	Phosphoserine Ref.11 Ref.12 Ref.13
	Modified residue	1818	1	Phosphoserine Ref.11 Ref.12 Ref.13
	Modified residue	1862	1	Phosphoserine Ref.13 Ref.14
	Modified residue	1889	1	Phosphoserine By similarity
	Modified residue	2067	1	Phosphoserine Ref.13
Natural variations
	Alternative sequence	1 – 14	14	Missing in isoform 3. Ref.4		VSP_050639
	Alternative sequence	680 – 731	52	Missing in isoform 3. Ref.4		VSP_050640
	Alternative sequence	843 – 845	3	LAA → RTR in isoform 3. Ref.4		VSP_050641
	Alternative sequence	846 – 2297	1452	Missing in isoform 3. Ref.4		VSP_050642
	Alternative sequence	1345 – 1381	37	Missing in isoform 2. Ref.5		VSP_050643
	Alternative sequence	2247 – 2261	15	DGALG…QVWFG → GSCGPRAVSTPTSYT in isoform 2. Ref.5		VSP_050644
	Alternative sequence	2248 – 2254	7	GALGTAR → PESEKPD in isoform 4. UniProtKB Q9JIH7		VSP_050645
	Alternative sequence	2255 – 2297	43	Missing in isoform 4. Ref.7		VSP_050646
	Alternative sequence	2262 – 2297	36	Missing in isoform 2. Ref.5		VSP_050647
	Natural variant	828	1	V → M. Corresponds to variant rs10761203 [ dbSNP | Ensembl ].		VAR_057114
	Natural variant	974	1	R → L. Corresponds to variant rs10114908 [ dbSNP | Ensembl ].		VAR_059773

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 2, 2004. Version 4. Checksum: 33D2EF2BFA6A1BD2	FASTA	2,297	242,676
	10 20 30 40 50 60 MDGDGGRRDV PGTLMEPGRG AGPAGMAEPR AKAARPGPQR FLRRSVVESD QEEPPGLEAA 70 80 90 100 110 120 EAPGPQPPQP LQRRVLLLCK TRRLIAERAR GRPAAPAPAA LVAQPGAPGA PADAGPEPVG 130 140 150 160 170 180 TQEPGPDPIA AAVETAPAPD GGPREEAAAT VRKEDEGAAE AKPEPGRTRR DEPEEEEDDE 190 200 210 220 230 240 DDLKAVATSL DGRFLKFDIE LGRGSFKTVY KGLDTETWVE VAWCELQDRK LTKLERQRFK 250 260 270 280 290 300 EEAEMLKGLQ HPNIVRFYDF WESSAKGKRC IVLVTELMTS GTLKTYLKRF KVMKPKVLRS 310 320 330 340 350 360 WCRQILKGLL FLHTRTPPII HRDLKCDNIF ITGPTGSVKI GDLGLATLKR ASFAKSVIGT 370 380 390 400 410 420 PEFMAPEMYE EHYDESVDVY AFGMCMLEMA TSEYPYSECQ NAAQIYRKVT CGIKPASFEK 430 440 450 460 470 480 VHDPEIKEII GECICKNKEE RYEIKDLLSH AFFAEDTGVR VELAEEDHGR KSTIALRLWV 490 500 510 520 530 540 EDPKKLKGKP KDNGAIEFTF DLEKETPDEV AQEMIESGFF HESDVKIVAK SIRDRVALIQ 550 560 570 580 590 600 WRRERIWPAL QPKEQQDVGS PDKARGPPVP LQVQVTYHAQ AGQPGPPEPE EPEADQHLLP 610 620 630 640 650 660 PTLPTSATSL ASDSTFDSGQ GSTVYSDSQS SQQSVMLGSL ADAAPSPAQC VCSPPVSEGP 670 680 690 700 710 720 VLPQSLPSLG AYQQPTAAPG LPVGSVPAPA CPPSLQQHFP DPAMSFAPVL PPPSTPMPTG 730 740 750 760 770 780 PGQPAPPGQQ PPPLAQPTPL PQVLAPQPVV PLQPVPPHLP PYLAPASQVG APAQLKPLQM 790 800 810 820 830 840 PQAPLQPLAQ VPPQMPPIPV VPPITPLAGI DGLPPALPDL PTATVPPVPP PQYFSPAVIL 850 860 870 880 890 900 PSLAAPLPPA SPALPLQAVK LPHPPGAPLA MPCRTIVPNA PATIPLLAVA PPGVAALSIH 910 920 930 940 950 960 SAVAQLPGQP VYPAAFPQMA PTDVPPSPHH TVQNMRATPP QPALPPQPTL PPQPVLPPQP 970 980 990 1000 1010 1020 TLPPQPVLPP QPTRPPQPVL PPQPMLPPQP VLPPQPALPV RPEPLQPHLP EQAAPAATPG 1030 1040 1050 1060 1070 1080 SQILLGHPAP YAVDVAAQVP TVPVPPAAVL SPPLPEVLLP AAPELLPQFP SSLATVSASV 1090 1100 1110 1120 1130 1140 QSVPTQTATL LPPANPPLPG GPGIASPCPT VQLTVEPVQE EQASQDKPPG LPQSCESYGG 1150 1160 1170 1180 1190 1200 SDVTSGKELS DSCEGAFGGG RLEGRAARKH HRRSTRARSR QERASRPRLT ILNVCNTGDK 1210 1220 1230 1240 1250 1260 MVECQLETHN HKMVTFKFDL DGDAPDEIAT YMVEHDFILQ AERETFIEQM KDVMDKAEDM 1270 1280 1290 1300 1310 1320 LSEDTDADRG SDPGTSPPHL STCGLGTGEE SRQSQANAPV YQQNVLHTGK RWFIICPVAE 1330 1340 1350 1360 1370 1380 HPAPEAPESS PPLPLSSLPP EASQGPCRGL TLPCLPWRRA ACGAVFLSLF SAESAQSKQP 1390 1400 1410 1420 1430 1440 PDSAPYKDQL SSKEQPSFLA SQQLLSQAGP SNPPGAPPAP LAPSSPPVTA LPQDGAAPAT 1450 1460 1470 1480 1490 1500 STMPEPASGT ASQAGGPGTP QGLTSELETS QPLAETHEAP LAVQPLVVGL APCTPAPEAA 1510 1520 1530 1540 1550 1560 STRDASAPRE PLPPPAPEPS PHSGTPQPAL GQPAPLLPAA VGAVSLATSQ LPSPPLGPTV 1570 1580 1590 1600 1610 1620 PPQPPSALES DGEGPPPRVG FVDSTIKSLD EKLRTLLYQE HVPTSSASAG TPVEVGDRDF 1630 1640 1650 1660 1670 1680 TLEPLRGDQP RSEVCGGDLA LPPVPKEAVS GRVQLPQPLV EKSELAPTRG AVMEQGTSSS 1690 1700 1710 1720 1730 1740 MTAESSPRSM LGYDRDGRQV ASDSHVVPSV PQDVPAFVRP ARVEPTDRDG GEAGESSAEP 1750 1760 1770 1780 1790 1800 PPSDMGTVGG QASHPQTLGA RALGSPRKRP EQQDVSSPAK TVGRFSVVST QDEWTLASPH 1810 1820 1830 1840 1850 1860 SLRYSAPPDV YLDEAPSSPD VKLAVRRAQT ASSIEVGVGE PVSSDSGDEG PRARPPVQKQ 1870 1880 1890 1900 1910 1920 ASLPVSGSVA GDFVKKATAF LQRPSRAGSL GPETPSRVGM KVPTISVTSF HSQSSYISSD 1930 1940 1950 1960 1970 1980 NDSELEDADI KKELQSLREK HLKEISELQS QQKQEIEALY RRLGKPLPPN VGFFHTAPPT 1990 2000 2010 2020 2030 2040 GRRRKTSKSK LKAGKLLNPL VRQLKVVASS TGHLADSSRG PPAKDPAQAS VGLTADSTGL 2050 2060 2070 2080 2090 2100 SGKAVQTQQP CSVRASLSSD ICSGLASDGG GARGQGWTVY HPTSERVTYK SSSKPRARFL 2110 2120 2130 2140 2150 2160 SGPVSVSIWS ALKRLCLGKE HSSRSSTSSL APGPEPGPQP ALHVQAQVNN SNNKKGTFTD 2170 2180 2190 2200 2210 2220 DLHKLVDEWT SKTVGAAQLK PTLNQLKQTQ KLQDMEAQAG WAAPGEARAM TAPRAGVGMP 2230 2240 2250 2260 2270 2280 RLPPAPGPLS TTVIPGAAPT LSVPTPDGAL GTARRNQVWF GLRVPPTACC GHSTQPRGGQ 2290 RVGSKTASFA ASDPVRS
	Isoform 2 [UniParc]. Checksum: BB5BC60D70A6E6D7	FASTA	2,224	234,948
	10 20 30 40 50 60 MDGDGGRRDV PGTLMEPGRG AGPAGMAEPR AKAARPGPQR FLRRSVVESD QEEPPGLEAA 70 80 90 100 110 120 EAPGPQPPQP LQRRVLLLCK TRRLIAERAR GRPAAPAPAA LVAQPGAPGA PADAGPEPVG 130 140 150 160 170 180 TQEPGPDPIA AAVETAPAPD GGPREEAAAT VRKEDEGAAE AKPEPGRTRR DEPEEEEDDE 190 200 210 220 230 240 DDLKAVATSL DGRFLKFDIE LGRGSFKTVY KGLDTETWVE VAWCELQDRK LTKLERQRFK 250 260 270 280 290 300 EEAEMLKGLQ HPNIVRFYDF WESSAKGKRC IVLVTELMTS GTLKTYLKRF KVMKPKVLRS 310 320 330 340 350 360 WCRQILKGLL FLHTRTPPII HRDLKCDNIF ITGPTGSVKI GDLGLATLKR ASFAKSVIGT 370 380 390 400 410 420 PEFMAPEMYE EHYDESVDVY AFGMCMLEMA TSEYPYSECQ NAAQIYRKVT CGIKPASFEK 430 440 450 460 470 480 VHDPEIKEII GECICKNKEE RYEIKDLLSH AFFAEDTGVR VELAEEDHGR KSTIALRLWV 490 500 510 520 530 540 EDPKKLKGKP KDNGAIEFTF DLEKETPDEV AQEMIESGFF HESDVKIVAK SIRDRVALIQ 550 560 570 580 590 600 WRRERIWPAL QPKEQQDVGS PDKARGPPVP LQVQVTYHAQ AGQPGPPEPE EPEADQHLLP 610 620 630 640 650 660 PTLPTSATSL ASDSTFDSGQ GSTVYSDSQS SQQSVMLGSL ADAAPSPAQC VCSPPVSEGP 670 680 690 700 710 720 VLPQSLPSLG AYQQPTAAPG LPVGSVPAPA CPPSLQQHFP DPAMSFAPVL PPPSTPMPTG 730 740 750 760 770 780 PGQPAPPGQQ PPPLAQPTPL PQVLAPQPVV PLQPVPPHLP PYLAPASQVG APAQLKPLQM 790 800 810 820 830 840 PQAPLQPLAQ VPPQMPPIPV VPPITPLAGI DGLPPALPDL PTATVPPVPP PQYFSPAVIL 850 860 870 880 890 900 PSLAAPLPPA SPALPLQAVK LPHPPGAPLA MPCRTIVPNA PATIPLLAVA PPGVAALSIH 910 920 930 940 950 960 SAVAQLPGQP VYPAAFPQMA PTDVPPSPHH TVQNMRATPP QPALPPQPTL PPQPVLPPQP 970 980 990 1000 1010 1020 TLPPQPVLPP QPTRPPQPVL PPQPMLPPQP VLPPQPALPV RPEPLQPHLP EQAAPAATPG 1030 1040 1050 1060 1070 1080 SQILLGHPAP YAVDVAAQVP TVPVPPAAVL SPPLPEVLLP AAPELLPQFP SSLATVSASV 1090 1100 1110 1120 1130 1140 QSVPTQTATL LPPANPPLPG GPGIASPCPT VQLTVEPVQE EQASQDKPPG LPQSCESYGG 1150 1160 1170 1180 1190 1200 SDVTSGKELS DSCEGAFGGG RLEGRAARKH HRRSTRARSR QERASRPRLT ILNVCNTGDK 1210 1220 1230 1240 1250 1260 MVECQLETHN HKMVTFKFDL DGDAPDEIAT YMVEHDFILQ AERETFIEQM KDVMDKAEDM 1270 1280 1290 1300 1310 1320 LSEDTDADRG SDPGTSPPHL STCGLGTGEE SRQSQANAPV YQQNVLHTGK RWFIICPVAE 1330 1340 1350 1360 1370 1380 HPAPEAPESS PPLPLSSLPP EASQDSAPYK DQLSSKEQPS FLASQQLLSQ AGPSNPPGAP 1390 1400 1410 1420 1430 1440 PAPLAPSSPP VTALPQDGAA PATSTMPEPA SGTASQAGGP GTPQGLTSEL ETSQPLAETH 1450 1460 1470 1480 1490 1500 EAPLAVQPLV VGLAPCTPAP EAASTRDASA PREPLPPPAP EPSPHSGTPQ PALGQPAPLL 1510 1520 1530 1540 1550 1560 PAAVGAVSLA TSQLPSPPLG PTVPPQPPSA LESDGEGPPP RVGFVDSTIK SLDEKLRTLL 1570 1580 1590 1600 1610 1620 YQEHVPTSSA SAGTPVEVGD RDFTLEPLRG DQPRSEVCGG DLALPPVPKE AVSGRVQLPQ 1630 1640 1650 1660 1670 1680 PLVEKSELAP TRGAVMEQGT SSSMTAESSP RSMLGYDRDG RQVASDSHVV PSVPQDVPAF 1690 1700 1710 1720 1730 1740 VRPARVEPTD RDGGEAGESS AEPPPSDMGT VGGQASHPQT LGARALGSPR KRPEQQDVSS 1750 1760 1770 1780 1790 1800 PAKTVGRFSV VSTQDEWTLA SPHSLRYSAP PDVYLDEAPS SPDVKLAVRR AQTASSIEVG 1810 1820 1830 1840 1850 1860 VGEPVSSDSG DEGPRARPPV QKQASLPVSG SVAGDFVKKA TAFLQRPSRA GSLGPETPSR 1870 1880 1890 1900 1910 1920 VGMKVPTISV TSFHSQSSYI SSDNDSELED ADIKKELQSL REKHLKEISE LQSQQKQEIE 1930 1940 1950 1960 1970 1980 ALYRRLGKPL PPNVGFFHTA PPTGRRRKTS KSKLKAGKLL NPLVRQLKVV ASSTGHLADS 1990 2000 2010 2020 2030 2040 SRGPPAKDPA QASVGLTADS TGLSGKAVQT QQPCSVRASL SSDICSGLAS DGGGARGQGW 2050 2060 2070 2080 2090 2100 TVYHPTSERV TYKSSSKPRA RFLSGPVSVS IWSALKRLCL GKEHSSRSST SSLAPGPEPG 2110 2120 2130 2140 2150 2160 PQPALHVQAQ VNNSNNKKGT FTDDLHKLVD EWTSKTVGAA QLKPTLNQLK QTQKLQDMEA 2170 2180 2190 2200 2210 2220 QAGWAAPGEA RAMTAPRAGV GMPRLPPAPG PLSTTVIPGA APTLSVPTPG SCGPRAVSTP TSYT
	Isoform 3 [UniParc]. Checksum: CC1BEDD3568635CD	FASTA	779	84,868
	10 20 30 40 50 60 MEPGRGAGPA GMAEPRAKAA RPGPQRFLRR SVVESDQEEP PGLEAAEAPG PQPPQPLQRR 70 80 90 100 110 120 VLLLCKTRRL IAERARGRPA APAPAALVAQ PGAPGAPADA GPEPVGTQEP GPDPIAAAVE 130 140 150 160 170 180 TAPAPDGGPR EEAAATVRKE DEGAAEAKPE PGRTRRDEPE EEEDDEDDLK AVATSLDGRF 190 200 210 220 230 240 LKFDIELGRG SFKTVYKGLD TETWVEVAWC ELQDRKLTKL ERQRFKEEAE MLKGLQHPNI 250 260 270 280 290 300 VRFYDFWESS AKGKRCIVLV TELMTSGTLK TYLKRFKVMK PKVLRSWCRQ ILKGLLFLHT 310 320 330 340 350 360 RTPPIIHRDL KCDNIFITGP TGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEHYD 370 380 390 400 410 420 ESVDVYAFGM CMLEMATSEY PYSECQNAAQ IYRKVTCGIK PASFEKVHDP EIKEIIGECI 430 440 450 460 470 480 CKNKEERYEI KDLLSHAFFA EDTGVRVELA EEDHGRKSTI ALRLWVEDPK KLKGKPKDNG 490 500 510 520 530 540 AIEFTFDLEK ETPDEVAQEM IESGFFHESD VKIVAKSIRD RVALIQWRRE RIWPALQPKE 550 560 570 580 590 600 QQDVGSPDKA RGPPVPLQVQ VTYHAQAGQP GPPEPEEPEA DQHLLPPTLP TSATSLASDS 610 620 630 640 650 660 TFDSGQGSTV YSDSQSSQQS VMLGSLADAA PSPAQCVCSP PVSEGPVLPQ SLPSLGAYQQ 670 680 690 700 710 720 PTAAPPPLAQ PTPLPQVLAP QPVVPLQPVP PHLPPYLAPA SQVGAPAQLK PLQMPQAPLQ 730 740 750 760 770 PLAQVPPQMP PIPVVPPITP LAGIDGLPPA LPDLPTATVP PVPPPQYFSP AVILPSRTR
	Isoform 4 [UniParc]. Checksum: 8C4E5F1DB7EAD99A	FASTA	2,254	238,279
	10 20 30 40 50 60 MDGDGGRRDV PGTLMEPGRG AGPAGMAEPR AKAARPGPQR FLRRSVVESD QEEPPGLEAA 70 80 90 100 110 120 EAPGPQPPQP LQRRVLLLCK TRRLIAERAR GRPAAPAPAA LVAQPGAPGA PADAGPEPVG 130 140 150 160 170 180 TQEPGPDPIA AAVETAPAPD GGPREEAAAT VRKEDEGAAE AKPEPGRTRR DEPEEEEDDE 190 200 210 220 230 240 DDLKAVATSL DGRFLKFDIE LGRGSFKTVY KGLDTETWVE VAWCELQDRK LTKLERQRFK 250 260 270 280 290 300 EEAEMLKGLQ HPNIVRFYDF WESSAKGKRC IVLVTELMTS GTLKTYLKRF KVMKPKVLRS 310 320 330 340 350 360 WCRQILKGLL FLHTRTPPII HRDLKCDNIF ITGPTGSVKI GDLGLATLKR ASFAKSVIGT 370 380 390 400 410 420 PEFMAPEMYE EHYDESVDVY AFGMCMLEMA TSEYPYSECQ NAAQIYRKVT CGIKPASFEK 430 440 450 460 470 480 VHDPEIKEII GECICKNKEE RYEIKDLLSH AFFAEDTGVR VELAEEDHGR KSTIALRLWV 490 500 510 520 530 540 EDPKKLKGKP KDNGAIEFTF DLEKETPDEV AQEMIESGFF HESDVKIVAK SIRDRVALIQ 550 560 570 580 590 600 WRRERIWPAL QPKEQQDVGS PDKARGPPVP LQVQVTYHAQ AGQPGPPEPE EPEADQHLLP 610 620 630 640 650 660 PTLPTSATSL ASDSTFDSGQ GSTVYSDSQS SQQSVMLGSL ADAAPSPAQC VCSPPVSEGP 670 680 690 700 710 720 VLPQSLPSLG AYQQPTAAPG LPVGSVPAPA CPPSLQQHFP DPAMSFAPVL PPPSTPMPTG 730 740 750 760 770 780 PGQPAPPGQQ PPPLAQPTPL PQVLAPQPVV PLQPVPPHLP PYLAPASQVG APAQLKPLQM 790 800 810 820 830 840 PQAPLQPLAQ VPPQMPPIPV VPPITPLAGI DGLPPALPDL PTATVPPVPP PQYFSPAVIL 850 860 870 880 890 900 PSLAAPLPPA SPALPLQAVK LPHPPGAPLA MPCRTIVPNA PATIPLLAVA PPGVAALSIH 910 920 930 940 950 960 SAVAQLPGQP VYPAAFPQMA PTDVPPSPHH TVQNMRATPP QPALPPQPTL PPQPVLPPQP 970 980 990 1000 1010 1020 TLPPQPVLPP QPTRPPQPVL PPQPMLPPQP VLPPQPALPV RPEPLQPHLP EQAAPAATPG 1030 1040 1050 1060 1070 1080 SQILLGHPAP YAVDVAAQVP TVPVPPAAVL SPPLPEVLLP AAPELLPQFP SSLATVSASV 1090 1100 1110 1120 1130 1140 QSVPTQTATL LPPANPPLPG GPGIASPCPT VQLTVEPVQE EQASQDKPPG LPQSCESYGG 1150 1160 1170 1180 1190 1200 SDVTSGKELS DSCEGAFGGG RLEGRAARKH HRRSTRARSR QERASRPRLT ILNVCNTGDK 1210 1220 1230 1240 1250 1260 MVECQLETHN HKMVTFKFDL DGDAPDEIAT YMVEHDFILQ AERETFIEQM KDVMDKAEDM 1270 1280 1290 1300 1310 1320 LSEDTDADRG SDPGTSPPHL STCGLGTGEE SRQSQANAPV YQQNVLHTGK RWFIICPVAE 1330 1340 1350 1360 1370 1380 HPAPEAPESS PPLPLSSLPP EASQGPCRGL TLPCLPWRRA ACGAVFLSLF SAESAQSKQP 1390 1400 1410 1420 1430 1440 PDSAPYKDQL SSKEQPSFLA SQQLLSQAGP SNPPGAPPAP LAPSSPPVTA LPQDGAAPAT 1450 1460 1470 1480 1490 1500 STMPEPASGT ASQAGGPGTP QGLTSELETS QPLAETHEAP LAVQPLVVGL APCTPAPEAA 1510 1520 1530 1540 1550 1560 STRDASAPRE PLPPPAPEPS PHSGTPQPAL GQPAPLLPAA VGAVSLATSQ LPSPPLGPTV 1570 1580 1590 1600 1610 1620 PPQPPSALES DGEGPPPRVG FVDSTIKSLD EKLRTLLYQE HVPTSSASAG TPVEVGDRDF 1630 1640 1650 1660 1670 1680 TLEPLRGDQP RSEVCGGDLA LPPVPKEAVS GRVQLPQPLV EKSELAPTRG AVMEQGTSSS 1690 1700 1710 1720 1730 1740 MTAESSPRSM LGYDRDGRQV ASDSHVVPSV PQDVPAFVRP ARVEPTDRDG GEAGESSAEP 1750 1760 1770 1780 1790 1800 PPSDMGTVGG QASHPQTLGA RALGSPRKRP EQQDVSSPAK TVGRFSVVST QDEWTLASPH 1810 1820 1830 1840 1850 1860 SLRYSAPPDV YLDEAPSSPD VKLAVRRAQT ASSIEVGVGE PVSSDSGDEG PRARPPVQKQ 1870 1880 1890 1900 1910 1920 ASLPVSGSVA GDFVKKATAF LQRPSRAGSL GPETPSRVGM KVPTISVTSF HSQSSYISSD 1930 1940 1950 1960 1970 1980 NDSELEDADI KKELQSLREK HLKEISELQS QQKQEIEALY RRLGKPLPPN VGFFHTAPPT 1990 2000 2010 2020 2030 2040 GRRRKTSKSK LKAGKLLNPL VRQLKVVASS TGHLADSSRG PPAKDPAQAS VGLTADSTGL 2050 2060 2070 2080 2090 2100 SGKAVQTQQP CSVRASLSSD ICSGLASDGG GARGQGWTVY HPTSERVTYK SSSKPRARFL 2110 2120 2130 2140 2150 2160 SGPVSVSIWS ALKRLCLGKE HSSRSSTSSL APGPEPGPQP ALHVQAQVNN SNNKKGTFTD 2170 2180 2190 2200 2210 2220 DLHKLVDEWT SKTVGAAQLK PTLNQLKQTQ KLQDMEAQAG WAAPGEARAM TAPRAGVGMP 2230 2240 2250 RLPPAPGPLS TTVIPGAAPT LSVPTPDPES EKPD

References

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[1]	"WNK kinases, a novel protein kinase subfamily in multi-cellular organisms." Verissimo F., Jordan P. Oncogene 20:5562-5569(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CHROMOSOMAL LOCATION. Tissue: Colon epithelium.
[2]	Jordan P. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Molecular basis of T cell-mediated recognition of pancreatic cancer cells." Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K. Cancer Res. 61:2038-2046(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-845 (ISOFORM 3). Tissue: Pancreatic cancer.
[5]	"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O. DNA Res. 7:347-355(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-2297 (ISOFORM 2). Tissue: Brain.
[6]	Ohara O., Nagase T., Kikuno R. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1609-2297 (ISOFORM 4). Tissue: Lung.
[8]	"Protein kinase WNK2 inhibits cell proliferation by negatively modulating the activation of MEK1/ERK1/2." Moniz S., Verissimo F., Matos P., Brazao R., Silva E., Kotelevets L., Kotevelets L., Chastre E., Gespach C., Jordan P. Oncogene 26:6071-6081(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION.
[9]	Erratum Moniz S., Verissimo F., Matos P., Brazao R., Silva E., Kotelevets L., Kotevelets L., Chastre E., Gespach C., Jordan P. Oncogene 27:155-155(2008)
[10]	"WNK2 modulates MEK1 activity through the Rho GTPase pathway." Moniz S., Matos P., Jordan P. Cell. Signal. 20:1762-1768(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1817 AND SER-1818, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1817 AND SER-1818, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"WNK2 is a novel regulator of essential neuronal cation-chloride cotransporters." Rinehart J., Vazquez N., Kahle K.T., Hodson C.A., Ring A.M., Gulcicek E.E., Louvi A., Bobadilla N.A., Gamba G., Lifton R.P. J. Biol. Chem. 286:30171-30180(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-45; SER-560; SER-1150; SER-1262; SER-1588; SER-1685; SER-1736; SER-1817; SER-1818; SER-1862 AND SER-2067.
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1862, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ242724 mRNA. Translation: CAB44308.5. AL390760, AL354991, AL583839 Genomic DNA. Translation: CAH73069.3. AL390760, AL354991, AL583839 Genomic DNA. Translation: CAH73070.2. AL583839, AL354991, AL390760 Genomic DNA. Translation: CAI12344.3. AL583839, AL354991, AL390760 Genomic DNA. Translation: CAI12345.2. AL354991, AL390760, AL583839 Genomic DNA. Translation: CAI14449.3. AL354991, AL390760, AL583839 Genomic DNA. Translation: CAI14450.2. AB044546 mRNA. Translation: BAB18648.1. AB051547 mRNA. Translation: BAB21851.2. BC037965 mRNA. Translation: AAH37965.1. Different initiation.
IPI	IPI00398808. IPI00398809. IPI00398811. IPI00796716.
RefSeq	NP_006639.3. NM_006648.3.
UniGene	Hs.654856.
3D structure databases
ProteinModelPortal	Q9Y3S1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y3S1. 8 interactions.
MINT	MINT-7241250.
STRING	9606.ENSP00000297954.
PTM databases
PhosphoSite	Q9Y3S1.
Polymorphism databases
DMDM	41688799.
Proteomic databases
PaxDb	Q9Y3S1.
PRIDE	Q9Y3S1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000297954; ENSP00000297954; ENSG00000165238.
GeneID	65268.
KEGG	hsa:65268.
UCSC	uc004ati.1. human. uc011lud.1. human.
Organism-specific databases
CTD	65268.
GeneCards	GC09P095947.
HGNC	HGNC:14542. WNK2.
MIM	606249. gene.
neXtProt	NX_Q9Y3S1.
PharmGKB	PA33783.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000139922.
HOVERGEN	HBG050345.
InParanoid	Q9Y3S1.
KO	K08867.
OMA	AFPQMAP.
PhylomeDB	Q9Y3S1.
Gene expression databases
ArrayExpress	Q9Y3S1.
Bgee	Q9Y3S1.
CleanEx	HS_WNK2.
Genevestigator	Q9Y3S1.
GermOnline	ENSG00000165238. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR024678. Kinase_OSR1/WNK_CCT. IPR000719. Prot_kinase_cat_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF12202. OSR1_C. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9Y3S1.
ChEMBL	CHEMBL5639.
GenomeRNAi	65268.
NextBio	67408.
SOURCE	Search...

Entry information

Entry name

WNK2_HUMAN

Accession

Primary (citable) accession number: Q9Y3S1
Secondary accession number(s): Q5VWF1 , Q5VWF2, Q8IY36, Q9C0A3, Q9H3P4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	February 2, 2004
Last modified:	May 1, 2013
This is version 120 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.